Key areas of comatose brains lose ability to coordinate activities.

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Neural imaging has helped change our perspective on what goes on in the brains of people who have lost consciousness for extended periods. Structural studies have shown that, while some people end up comatose or vegetative because of significant structural damage, others remain unconscious despite having brains that appear largely intact. And, in a recent case, a patient who has been categorized as vegetative for over a decade showed brain activity that suggested he was responding to researchers' queries.

These findings suggest that there may be two ways to end up comatose: either through physical damage to the brain, or because key areas of the brain are no longer able to coordinate their activities. A paper published in yesterday's PNAS provides further support to this latter proposition, but the authors don't seem to go as far as they could in supporting it.

The researchers had permission to track the activity of the brains of 17 people with "severely impaired consciousness" due to a non-neural medical conditions (they generally lost consciousness due to cardiac and/or respiratory failure). 20 healthy individuals volunteered to act as controls.

The activity in each of 417 anatomically defined brain regions was tracked using functional MRI, after which a computerized analysis was done to see which areas were active at similar times. More specifically, every single region was compared pairwise to all 416 of the other regions, with wavelet analysis being used to detect correlations in activity. That data was used to establish links among different regions, and the results were then subjected to network analysis, which identified features like the degree of global connectivity and the location of key hubs in the network.

On a gross level, the measures of network structure all looked very similar between healthy and comatose individuals. Measures like the degree of clustering and the modularity were all within statistical error between the two groups. If the analysis had stopped there, you'd have to conclude that unconsciousness changes very little.

But the researchers didn't stop there. They developed a measure that represented the degree to which each brain region acted as a hub, forming connections with a cluster of other regions with coordinated activity. They then confirmed that the regions identified as hubs were generally similar in both of the two populations (volunteers and patients). This suggested that the measure they had developed actually reflected something about the brain activity.

With that validation in hand, they compared the two populations. And that's where a big difference became apparent: areas that had been hubs in healthy people were no longer central in the comatose, and vice versa. Or, as the authors put it, "The nodes that had the highest hubness scores in healthy volunteers showed the greatest reduction in patients, whereas the nodes that had the lowest hubness scores in healthy volunteers showed the greatest increase in patients."

This implies that different areas of the brain are talking to each other in comatose patients. This supports the idea that the loss of consciousness in these patients may result (at least in part) from the fact that key areas of the brain are no longer coordinating their activity in a way that can enable conscious actions.

The authors note a number of appropriate cautions for functional MRI studies: a small population, the danger of small shifts in position causing anatomical structures to be misidentified, and so on. In general, they suggest that these probably weren't sufficient to throw their conclusions off.

But they missed a big opportunity to help validate their data. We already have plenty of anatomic studies that show which areas are physically linked to others in the brain and, in many cases, there is functional evidence that shows that these connected regions coordinate their activity. This information should give the researchers the opportunity to see if their wavelet analysis was actually capturing what we already know about biology. For whatever reasons, they didn't do it.